1. Field
The invention relates to a new process for the preparation of retiferol derivatives of the formula: ##STR2##
wherein PA1 A is --C.ident.C-- or --CH.dbd.CH--, and PA1 R.sup.1 and R.sup.2 are independently of each other lower alkyl or lower perfluoroalkyl. PA1 wherein PA1 A is --C.ident.C-- or --CH.dbd.CH--, and PA1 R.sup.1 and R.sup.2 are independently of each other lower alkyl or lower perfluoroalkyl. PA1 method A which comprises the coupling of ketones of formula II with compounds of formula III or by PA1 method B which comprises the coupling of phosphinoxides of formula IV with aldehydes of formula V, PA1 wherein A, R.sup.1 and R.sup.2 are as defined above and PA1 X.sup.1, R.sup.2 and Y are hydroxy protecting groups PA1 for X.sup.1 and X.sup.2 independently of each other a mono alkyl dimethyl-silyl group [Si(C.sub.1-4 -alkyl)Me.sub.2 ], preferably a tert-butyldimethyl-silyl group (TBS) or an acyl group (R.sup.3 CO--), wherein R.sup.3 signifies lower alkyl or mono chlorinated lower alkyl; and for Y a trialkyl-silyl group [Si(C.sub.1-4 -alkyl).sub.3 ], preferably a triethyl-silyl group (SiEt.sub.3) or a trimethyl-silyl group (SiMe.sub.3). PA1 method A, which comprises the coupling of ketones of formula II with compounds of formula III or by PA1 method B, which comprises the coupling of phosphinoxides of formula IV with aldehydes of formula V. PA1 wherein R.sup.3 is lower alkyl or mono chlorinated lower alkyl except the tert-butyl group. PA1 wherein the symbols are as defined above and R.sup.3 is a methyl group. PA1 wherein the symbols are as defined above. PA1 wherein the symbols are as defined above and R.sup.5 is lower alkyl. PA1 where the symbols are as defined above. PA1 wherein R.sup.3 signifies lower alkyl or mono chlorinated lower alkyl and R.sup.4 is a mono alkyl dimethyl-silyl group [Si(C.sub.1-4 -alkyl)Me.sub.2 ]. PA1 wherein the symbols are as defined above and R.sup.4 is a mono alkyl dimethyl-silyl group [Si(C.sub.1-4 -alkyl)Me.sub.2 ], preferably a mono (C.sub.1 -C.sub.4) alkyl dimethyl-silyl group [Si(C.sub.1-4 -alkyl)Me.sub.2 ], especially preferred is a tert-butyldimethyl-silyl group (TBS). PA1 method A (steps 1.1-1.2) which comprises the coupling of ketones of formula II with compounds of formula III or by PA1 method IB (steps 6.1-6.2) which comprises the coupling of phosphinoxides of formula IV with aldehydes of formula V. PA1 step 2.1-2.3 via an enzymatic hydrolyzation reaction or PA1 step 3.1-3.5 via an enzymatic acylation reaction.
2. Description
Compounds of formula I can be utilized to treat or prevent hyperproliferative skin diseases such as psoriasis, basal cell carcinomas, disorders of keratinization and keratosis neoplastic diseases and disorders of the sebaceous glands such as acne and seborrhoic dermatitis. The compounds of formula I can also be utilized in reversing the conditions associated with photodamage, particularly for the oral or topical treatment of the skin damaged through sun exposure, the effects of wrinkling, elastosis and premature aging, especially for the treatment of psoriasis. Such compounds are known and disclosed in WO 99/43646.